Intestinal CD8+ T cell responses are abundantly induced early in human development but show impaired cytotoxic effector capacities

Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8(+) T cells are critical to achieve viral control. However, studies investigating the development of CD8(+) T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8(+) T cell compartment in human fetal, infant and adult intestinal tissues. CD8(+) T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7(-)CD45RA(-)CD127(-)KLRG1(+/-) CD8(+) T cells compared to tissue-resident memory CD69(+)CD103(+)CD8(+) T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8(+) T cells was, however, markedly reduced compared to adult intestinal CD8(+) T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8(+) T cells. Taken together, we demonstrate that intestinal CD8(+) T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8(+) T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.

Automated summary

The study found that CD8(+) T cell responses in the early human gut are induced but exhibit reduced functionality compared to adults. This decreased functionality may contribute to increased tolerance to foreign antigens after birth, and subsequently increase susceptibility to gastrointestinal viral infections in infancy.